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Introduction: Cardiovascular disease is the leading cause of death in California (CA) and social determinants of health accounts for some of the geographic variations in cardiovascular disease (CVD) prevalence and mortality. However, the association between place-based social disadvantage indices and CVD prevalence has not been extensively studied. Objective/Hypothesis: To examines the association between zip code level social disadvantage indices and CVD prevalence in CA. We hypothesized that zip codes with high social disadvantage will have higher prevalence of CVDs. Methods: In this retrospective cross-sectional study, we linked the zip code level crude prevalence rate of CVD among persons 18 years and older in CA for 2022 with their corresponding scores for Social Vulnerability Index (SVI), Healthy Places Index (HPI), and Social Vulnerability Metric (SVM). These indices are computed variable sets of sociodemographic data for each zip code. The CVD prevalence data was obtained from the UCLA Center for Health Policy. Zip codes without CVD prevalence data were excluded. The linked dataset was divided into quartiles based on the individual index scores with quartile 1 (Q1) representing the least disadvantaged and quartile 4 (Q4) representing the most disadvantaged zip codes. For each index, we estimated the mean CVD prevalence (expressed as proportion) with 95% confidence intervals (CI) for each quartile. The outcome was the difference in prevalence between Q4 and Q1 and this was significant if the CIs did not overlap. Results: Among 1,275 zip codes in CA, the overall CVD prevalence rate was 7.6% (CI: 7.5-7.7). For all three indices, there was a stepwise decrease in the CVD prevalence with increasing social disadvantage quartile. For SVI, the prevalence was significantly higher in Q1 (9.03%, CI: 8.7-9.4) than Q4 (6.4%, CI: 6.3-6.5). The trend was the similar for SVM (Q1: 8.4%, CI: 8.3-8.6; Q4: 6.6%, CI: 6.4-6.9) and HPI (Q1: 8.4%, CI: 8.1-8.6; Q4: 6.4%, CI: 6.2-6.5). Conclusion: Contrary to our hypothesis and the results of previous studies, we found that no association between high social disadvantage as measured by three different indices and CVD prevalence at the zip code level in CA. The results of this study need further inquiry and validation